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Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
Several Ames Tests, 2 chromosome aberrations(CA) tests, 2 HPRT test, a sister chromatid exchange assay, an in-vitro MNT and an UDS test in vitro are available. Additional, in vivo micronucleus tests(MNT) in rat bone, MNTs in mouse rat bone and blood and a test for the detection of carcinogen-induced sperm head abnormalities in mice are available.
Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and sufficient documented
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Principles of method if other than guideline:
In a bone marrow micronucleus evaluations, male F344/N rats received three intraperitoneal injections of m-chloroaniline dissolved in corn oil at 24-hour intervals. The total dosing volume was 0.4 mL. Solvent control rats were injected with corn oil only; the positive control animals received injections of 25 mg/kg cyclophosphamide. Twenty-four hours after the final injection, the animals were killed and smears of the bone marrow cells obtained from the femurs were prepared. Air-dried smears were fixed and stained; 2,000 polychromatic erythrocytes (PCEs) were scored for frequency of micronucleated cells in each of five animals per dose group. In addition, the percentage of PCEs among the total erythrocyte population in the bone marrow was scored for each dose group as a measure of toxicity.
GLP compliance:
yes
Type of assay:
micronucleus assay
Test material information:
Composition 1
Species:
rat
Strain:
Fischer 344
Sex:
male
Route of administration:
intraperitoneal
Duration of treatment / exposure:
three intraperitoneal injections at 24-hour interval
Frequency of treatment:
three intraperitoneal injections at 24-hour interval
Post exposure period:
twenty-four hours after the final injection, the animals were killed
Remarks:
Doses / Concentrations:
25 or 1000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
5 animals per dose
Control animals:
yes, concurrent vehicle
Tissues and cell types examined:
bone marrow cells of F344/N rats
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes

Results from the in vivo rat bone marrow micronucleus tests with m-chloroaniline were negative. In the single trial performed with male rats, only two dose groups survived, but these were sufficient for a valid test; no significant increase in the number of micronucleated erythrocytes was observed in rats.

Conclusions:
Interpretation of results (migrated information): negative
Executive summary:

In a bone marrow micronucleus evaluations, male F344/N rats received three intraperitoneal injections of m-chloroaniline dissolved in corn oil at 24-hour intervals. The total dosing volume was 0.4 mL. Solvent control rats were injected with corn oil only; the positive control animals received injections of 25 mg/kg cyclophosphamide. Twenty-four hours after the final injection, the animals were killed and smears of the bone marrow cells obtained from the femurs were prepared. Air-dried smears were fixed and stained; 2,000 polychromatic erythrocytes (PCEs) were scored for frequency of micronucleated cells in each of five animals per dose group. In addition, the percentage of PCEs among the total erythrocyte population in the bone marrow was scored for each dose group as a measure of toxicity.

The results from the in vivo rat bone marrow micronucleus tests with m-chloroaniline were negative.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

All Ames test in salmonella typhimurium strains were negative but one assay with metabolic activation and co-treatment with norharmane m-chloroaniline was positive. Without activation in presence of norharmane the test was negative. Aspergillus nidulans revealed a slight positive result.

In one CA (CHO cells) m-chloronailine was negative whereas the other test (with CHL cells) was positive. In one HPRT test,

m-chloroaniline was positive in L5178Y mouse lymphoma cells with and without metabolic activation. Additional, the mutagenic activity of m-chloroaniline on 8AG (8-azaguanine) and OUA (ouabain) mutations in chinese hamster V79 cells was examined. m-chloroaniline was positive on 8AG and negative on OUA. An in-vitro MNT was positive.

In rat hepatocyte culture m-chloroaniline was tested for unscheduled DNA synthesis (UDS). m-chloroaniline was negative in this UDS asssay at a concentration of 50 nmole/ml.

All in-vivo MNTs m-chloroaniline was negative. Also is the test for the detection of sperm-head abnormalities m-chloroaniline was negative.


Justification for selection of genetic toxicity endpoint
Several Ames Tests, 2 chromosome aberrations twests, 2 HPRT test, a sister chromatid exchange assay, an in-vitro MNT and an UDS test in vitro are available. Additional, in vivo micronucleus tests(MNT) in rat bone, MNTs in mouse rat bone and blood and a test for the detection of carcinogen-induced sperm head abnormalities in mice are available.

Justification for classification or non-classification

There are nagative and some positive in-vitro assays, but all in-vivo assays were negative. Therefore a classification is not justified.